To assess the safety and to evaluate the anti-HIV effect of low-, moderate-, and high-dose schedules of zidovudine (AZT) plus didanosine (ddI) versus ddI alone in asymptomatic HIV-infected patients. Because of the failure with long-term (more than 1 year) use of, frequency of toxicity from, and drug resistance to AZT, drug combinations need to be developed to enable lower, less toxic doses of AZT to be used and to slow or prevent the development of resistance, while providing at least the same effectiveness.

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

116

Study Completion Date:

November 1993

Detailed Description:

Because of the failure with long-term (more than 1 year) use of, frequency of toxicity from, and drug resistance to AZT, drug combinations need to be developed to enable lower, less toxic doses of AZT to be used and to slow or prevent the development of resistance, while providing at least the same effectiveness.

Enrollment during the first 8 weeks of the study is restricted to hemophiliacs and sexual partners of hemophiliacs with asymptomatic HIV disease. After the initial 8 weeks this restriction is lifted. Patients are randomized to one of four treatment arms with dosing of AZT plus ddI or ddI alone.

Eligibility

Ages Eligible for Study:

12 Years and older (Child, Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

Aerosolized pentamidine.

Acute and intermittent therapy with mycostatin and mycelex.

Isoniazid, if no alternative therapy is available.

Allowed for up to 2 weeks:

Acyclovir for Herpes infection (withhold didanosine during therapy).

Acute therapy with fluconazole or ketoconazole.

Allowed but preferably not on a continuous basis for > 72 hours:

Acetaminophen.

Ibuprofen.

Nonsteroidal antiinflammatory agents.

Patients must be:

HIV antibody positive.

Asymptomatic or have persistent generalized lymphadenopathy.

Diagnosed with one of the listed coagulopathies.

OR Sexual partner of someone with the above criteria.

Allowed:

Basal cell carcinoma or in situ carcinoma of the cervix.

NOTE:

As of January, 1991 full accrual of patients with prior AZT use has been reached - NOW ACCRUING ONLY THOSE WITH NO PRIOR AZT USE. Hemophilia restriction has been lifted.

Prior Medication:

Allowed:

Zidovudine (AZT) for a total of = or < 13 months.

NOTE:

As of January, 1991 accrual of these patients was reached, NOW ONLY PATIENTS WITH NO PRIOR AZT.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

Unexplained temperature > 38 degrees C for more than 5 consecutive days or on more than 10 days in any 30-day period in the 2 years prior to study entry.

Unexplained diarrhea defined as at least 3 liquid stools/day persisting more than 7 days within 2 years prior to study entry.

Grade 2 or higher neuropathy based on the Neuropathy Targeted Symptom Questionnaire.

Seizures.

Zidovudine therapy for = or > 13 months.

Heart disease.

Psychological or emotional problems sufficient in the investigator's opinion to prevent adequate compliance with study therapy.

Gout.

Prior Medication:

Excluded within 4 weeks of study entry:

Antiretroviral agents, including ribavirin, HPA-23, rifampin, AL721.

Excluded within 3 months of study entry:

Significant course of immunomodulating agents, such as steroids (> 1 week), isoprinosine, thymic factors, or any other experimental drugs.

Excluded within 30 days prior to study entry:

Neurotoxic drugs.

Excluded:

Didanosine (ddI).

Dideoxycytidine (ddC).

Zidovudine (AZT) if received for > 13 months.

Prior Treatment:

Excluded within 3 months of entry:

Other experimental therapy.

History of recent alcohol abuse.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000656